CN104130243A - Substituted p-halogenophenyl triazole ring substituted nicotinamide fluoride compounds and synthesis method thereof - Google Patents

Substituted p-halogenophenyl triazole ring substituted nicotinamide fluoride compounds and synthesis method thereof Download PDF

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CN104130243A
CN104130243A CN201410322983.0A CN201410322983A CN104130243A CN 104130243 A CN104130243 A CN 104130243A CN 201410322983 A CN201410322983 A CN 201410322983A CN 104130243 A CN104130243 A CN 104130243A
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niacinamide
triazole
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CN104130243B (en
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岳刚
关登仕
杨世琰
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Hebei Maison Chemical Co Ltd
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles

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Abstract

The invention provides substituted p-halogenophenyl triazole ring substituted nicotinamide fluoride compounds with a structural general formula represented as the following. Because the compounds provided by the invention comprise p-halogenophenyl triazole ring, on the whole the compounds (III), (IV), (V), and (VI) provided by the invention have a similar structure with that of boscalid (VII). Theoretically the compounds have predictable antibacterial activities. On the basis that original boscalid bond length and agrochemical activity as a bactericide are maintained, through replacing key substituent wherein -Cl in nicotinamide group is replaced by using Rf which is -F or -CFH2, the life with a same dose in field is prolonged, because fluorocarbon bond is stronger than chlorocarbon bond.

Description

Replacement replaces and fluoridizes niacinamide compound and synthetic method halobenzene base triazole ring
Technical field
The present invention relates to a kind of replacement halobenzene base triazole ring is replaced and fluoridizes niacinamide compound and synthetic method, belong to Synthetic Organic Chemistry technical field.
Background technology
The whole world is to ecotope in recent years, and medical supplies etc. are directly with indirectly more and more higher to the cry of food contamination, and the development investment of medical supplies and product for agriculture new variety is increasing, and the corresponding management department reviews of national governments is more and more stricter.The teratogenesis of product innovation, carcinogenic and the impact of ecotope is observed is not can fully understand in a short time, so developer, investor and production firm be more and more be primarily focused on existing efficient, environmentally friendly, the product of cost performance excellence carries out structure of modification, or develops pre-composition to meet growing demand on original basis.Improvement and development due to chemical theory and production technique, agricultural chemicals is synthetic at present can be related to rule according to the structure and properties of active substance molecule, according to Agrochemicals, need to design nature non-existent, new, highly active, and the agricultural chemicals good with Environmental compatibility, design philosophy of the present invention is exactly on the basis of existing disinfectant use in agriculture boscalid amine (Boscalid or the title chloro-N-of 2-(4-chlordiphenyl-2-yl) niacinamide), by replacing crucial substituting group, obtain the compound that a class is new, and predict its application direction.
Boscalid amine (Boscalid or the title chloro-N-of 2-(4-chlordiphenyl-2-yl) niacinamide) chemical structural formula represents as schemed (VII):
Summary of the invention
The object of the invention is to the contrary analytical procedure synthetic according to organic compound, utilize synthetic chemistry selectivity strategy, build two three keys of carbon carbon list, solve the stereochemistry composition problem of target compound, synthetic a kind of replacements to halobenzene base triazole ring replacement fluoridize niacinamide compound, and expect the theoretic fungicidal activity of this compound and application direction.
Technical scheme of the present invention is achieved in that this replacement replaces and to fluoridize niacinamide compound halobenzene base triazole ring, and compound structure represents as general formula:
Wherein:
A is N-(1-replaces halobenzene base-1,2,3-triazoles)-5-amine groups:
Or
A is N-(5-replaces halobenzene base-1,2,4-triazole)-3-amine groups:
-R is-F ,-Cl ,-Br ,-CFH 2,-CF 2h.
Described replacement replaces and fluoridizes niacinamide compound halobenzene base triazole ring, the compound of structure formula I is that (1-replaces halobenzene base-1 N-, 2,3-triazole-5-yl)-2-fluorine niacinamide, wherein the replacement of 1-position is respectively fluorobenzene halobenzene base, to chlorobenzene, to bromobenzene, to methyl fluoride benzene, to benzal fluoride; R ffor-F; Compound structure represents as led to formula III:
Described replacement replaces and fluoridizes niacinamide compound halobenzene base triazole ring, the compound of structure formula I is that (1-replaces halobenzene base-1 N-, 2,3-triazole-5-yl)-2-methyl fluoride niacinamide, wherein the replacement of 1-position is respectively fluorobenzene halobenzene base, to chlorobenzene, to bromobenzene, to methyl fluoride benzene, to benzal fluoride; R ffor-CFH 2; Be that compound structure represents as led to formula IV:
Described replacement replaces and fluoridizes niacinamide compound halobenzene base triazole ring, the compound of structure formula II is N-(5-substituted-phenyl-1,2,4-triazole-3-yl)-2-fluorine niacinamide, wherein, the replacement of 5-position is respectively fluorobenzene halobenzene base, to chlorobenzene, to bromobenzene, to methyl fluoride benzene, to benzal fluoride; R ffor-F; Compound structure represents as general formula (V):
Described replacement replaces and fluoridizes niacinamide compound halobenzene base triazole ring, the compound of described structure formula II is N-(5-substituted-phenyl-1,2,4-triazole-3-yl)-2-methyl fluoride niacinamide, wherein, the replacement of 5-position is respectively fluorobenzene halobenzene base, to chlorobenzene, to bromobenzene, to methyl fluoride benzene, to benzal fluoride; R ffor-CFH 2; Compound structure represents as led to formula VI:
Described replacement replaces the synthetic method of fluoridizing niacinamide compound to halobenzene base triazole ring, wherein the synthesis step of N-(1-is to fluorophenyl-1,2,3-triazoles-5-yl)-2-fluorine niacinamide (III) comprising:
A, synthetic 1-, to fluorophenyl-5-amido-1,2,3-triazoles, react as follows:
A-1, by 1.1 grams of para-fluoroaniline, 0.01 mole is dissolved in 30 milliliters of 2M hydrochloric acid, add 40 ml water dilutions, again by 0.7 gram of Sodium Nitrite, 0.01 mole is dissolved in a small amount of water, and reaction makes diazonium salt solution at 0 ℃, maintains this temperature and drips amido acetonitrilehydrochlorate 1.0g, the 30 ml water solution of 0.01 mole, stirring reaction 2 hours;
A-2, add standing over night after excessive sodium acetate 25-30 gram dissolving, petroleum ether extraction obtains crude product, then recrystallization obtains 1-to 1.9 grams of fluoro-azidophenyl-3-nitrile methyl-triazenes (A), fusing point 95-96 ℃, yield 95% in sherwood oil;
A-3, above-mentioned triazene is dissolved in non-protonic solvent methylene dichloride, add 5 grams of alkali aluminas, it does not dissolve, and within being suspended in solvent, under room temperature, stirring and spends the night, elimination solid, desolventize target compound 1-to 1.6 grams of fluorophenyl-5-amido-1,2,3-triazoles, 130 ℃ of fusing points, yield 80%;
B, synthetic N-(1-is to fluorophenyl-1,2,3-triazoles-5-yl)-2-fluorine niacinamide, react as follows:
B-1, by 1.5 grams, the fluorine-based nicotinic acid of 2-, 0.01 mole, be added to 6.0 grams of excessive thionyl chlorides, in 0.05 mole, chlorine and sulfurous gas are discharged in reaction at once, react mild post-heating and reflux 1 hour, decompression, except excessive thionyl chloride, makes acyl chlorides;
B-2,1-that A-3 is made are to 1.7 grams of fluorophenyl-5-amido-1,2,3-triazoles, 0.009 mole of 30 milliliters of dichloromethane solution, is slowly added drop-wise in the 2-fluorine nicotinoyl chlorine making, and dropwises and continues to stir 30 minutes, desolventize, by 1M aqueous sodium hydroxide washes, wash and be neutral;
B-3, benzene extraction, dry rear with alcohol crystal, purifying obtains 2.4 grams of N-(1-is to fluorophenyl-1,2,3-triazoles-5-yl)-2-fluorine niacinamide colourless crystallization, fusing point 165.2-166.3 ℃.
Described replacement replaces the synthetic method fluoridize niacinamide compound to halobenzene base triazole ring, wherein the synthesis step of N-(5-to fluorophenyl-1,2,4-triazole-3-yl)-2-fluorine niacinamide (V) comprising:
A, synthetic 5-be to amido-1, fluorophenyl-3, and 2,4-triazole is reacted as follows:
A-1, by 11.2 grams of p-Fluorobenzenecarboxaldehydes, 0.09 mole is dissolved in 100 milliliters of benzene, adds 11.5 grams of trifluoroacetyl hydrazines, 0.09 mole, under room temperature, stir 12 hours, obtain 21.1 grams of product trifluoroacetyl group hydrazones, 0.09 mole, except desolventizing, product is not purified can directly be used;
A-2, by 20.0 grams of N-succinic diamide muriates (NCS), 50 milliliters of methylene dichloride of 0.15 mole add 18.6 grams of dimethyl thioethers (DMS) at 0 ℃, 0.30 mole, obtain NCS-DMS complex compound after stirring half an hour; 21.1 grams of the trifluoroacetyl group hydrazones that A-1 is made, 50 milliliters of dichloromethane solutions of 0.09 mole react 1 hour with NCS-DMS complex compound at-78 ℃, under stirring, slowly rise to room temperature and react 6 hours, making the methyne chloride derivatives solution of trifluoroacetyl hydrazone; After product desolventizes, cross silicagel column, use irrigation sherwood oil: ethyl acetate=98: 2-98: 10, desolventizing obtains 14.8 grams, the muriatic derivative of pure methyne, 0.05 mole;
A-3,50 milliliters of acetonitrile solutions of steps A-2 methyne muriate add 4.8 grams, urea; 10.0 grams of 0.08 mole and excessive triethylamines; under 0.1 mole of room temperature, stir 12 hours; washing desalination obtains 17.5 grams of trifluoroacetyl hydrazone urea derivatives (B); 0.06 mole; thick 42.4 grams of excess of sodium carbonate for product; under 100 milliliters of room temperatures of 1: 1 aqueous ethanolic solution of 0.4 mole, stir 2 hours cyclodehydrations and remove protecting group trifluoroacetyl group simultaneously; obtain target compound 5-to fluorophenyl-3-amido-1; 8.4 grams of 2,4-triazoles, fusing point; 125 ℃, yield 78%.
B, synthetic N-(5-to fluorophenyl-1,2,4-triazole-3-yl)-2-fluorine niacinamide, reacts as follows:
B-1, by 1.5 grams, the fluorine-based nicotinic acid of 2-, 0.01 mole is added to 6.0 grams of excessive thionyl chlorides, in 0.05 mole, chlorine and sulfurous gas are discharged in reaction at once, notice that water absorbs in order to avoid poisoning, react mild post-heating and reflux 1 hour, decompression, except excessive thionyl chloride, makes acyl chlorides;
B-2,5-that A-3 step is obtained be to fluorophenyl-3-amido-1,1.7 grams of 2,4-triazoles, 30 milliliters of chloroformic solutions of 0.009 mole, are slowly added drop-wise in the fluorine-based nicotinoyl chlorine of the 2-making, after dropwising, continue to stir 30 minutes, desolventize by 1M aqueous sodium hydroxide washes and wash and be neutral;
The extraction of B-3, benzene, dry after with alcohol crystal, after purifying, obtain 2.0 grams of target compound N-(5-to fluorophenyl-1,2,4-triazole-3-yl)-2-fluorine niacinamide colourless crystallizations, fusing point 161.8-162.8 ℃.
Described replacement replaces the purposes fluoridize niacinamide compound to halobenzene base triazole ring, for effective constituent or the ancillary component of agricultural bactericidal preparation or make mixed preparation with other effective constituents.
Replacement disclosed by the invention replaces and fluoridizes niacinamide compound owing to containing triazole ring halobenzene base triazole ring, compound of the present invention (III) on the whole, (IV), (V), (VI) and boscalid amine (VII) structural similitude, also can claim that it is class boscalid amine (Similar Boscalid), has predictable fungicidal activity in theory.The present invention is maintaining on the bond distance and the active basis of agrochemicals as sterilant of original boscalid amine, by replacing crucial substituting group, with Rf=-F, replaced in niacinamide group-Cl of-CFH2, because fluorine carbon bond is stronger than chlorine carbon bond, make the middle ILS using with dosage afield.In addition due to (III), (IV), (V), (VI) is containing the impact of triazole ring nitrogen-atoms, this two kinds boscalid amine solubleness in strong solvent (as low-carbon alcohol and water) increases, for the strong solvent as agricultural bactericidal agent formulation provides good basis.
Embodiment
Below in conjunction with the drawings and specific embodiments, the present invention is further detailed explanation.
Only with N-, replace halobenzene base triazole ring is replaced and fluoridizes niacinamide compound as structure formula III below, (IV), synthetic method shown in (V) and (VI), enumerate two representative embodiment:
Embodiment 1, and the N-of structure formula III (1-is to fluorophenyl-1,2,3-triazoles-5-yl)-2-fluorine niacinamide is synthetic, and R is F, and Rf is F
A, 1-are synthetic to fluorophenyl-5-amido-1,2,3-triazoles, and reaction and step are as follows:
A-1, by 1.1 grams of para-fluoroaniline, 0.01 mole is dissolved in 30 milliliters of 2M hydrochloric acid, add 40 ml water dilutions, again by 0.7 gram of Sodium Nitrite, 0.01 mole is dissolved in a small amount of water, and reaction makes diazonium salt solution at 0 ℃, maintains this temperature and drips amido acetonitrilehydrochlorate 1.0g, the 30 ml water solution of 0.01 mole, stirring reaction 2 hours;
A-2, add standing over night after excessive sodium acetate 25-30 gram dissolving, petroleum ether extraction obtains crude product, then recrystallization obtains 1-to 1.9 grams of fluoro-azidophenyl-3-nitrile methyl-triazenes (A), fusing point 95-96 ℃, yield 95% in sherwood oil;
A-3, above-mentioned triazene is dissolved in non-protonic solvent methylene dichloride, add 5 grams of alkali aluminas, it does not dissolve, and within being suspended in solvent, under room temperature, stirring and spends the night, elimination solid, desolventize target compound 1-to 1.6 grams of fluorophenyl-5-amido-1,2,3-triazoles, 130 ℃ of fusing points, yield 80%;
Because be similar to the reactivity worth of halobenzene amine, the method for therefore continuing to use embodiment 1 can obtain different 1-and replace halobenzene base-5-amido-1,2,3-triazoles compound, as shown in table 1:
Table 1 1-replaces halobenzene base-5-amido-1,2,3-triazoles
Building-up reactions and the step of B, N-(1-is to fluorophenyl-1,2,3-triazoles-5-yl)-2-fluorine niacinamide:
B-1, by 1.5 grams, the fluorine-based nicotinic acid of 2-, 0.01 mole, be added to 6.0 grams of excessive thionyl chlorides, in 0.05 mole, chlorine and sulfurous gas are discharged in reaction at once, react mild post-heating and reflux 1 hour, decompression, except excessive thionyl chloride, makes acyl chlorides;
B-2,1-that A-3 is made are to 1.7 grams of fluorophenyl-5-amido-1,2,3-triazoles, 0.009 mole of 30 milliliters of dichloromethane solution, is slowly added drop-wise in the 2-fluorine nicotinoyl chlorine making, and dropwises and continues to stir 30 minutes, desolventize, by 1M aqueous sodium hydroxide washes, wash and be neutral;
B-3, benzene extraction, dry rear with alcohol crystal, purifying obtains 2.4 grams of N-(1-is to fluorophenyl-1,2,3-triazoles-5-yl)-2-fluorine niacinamide colourless crystallization, fusing point 165.2-166.3 ℃.
The B step reaction of above-described embodiment 1 comprise different 2-containing the chloride product of fluoro substituents (fluorine-based and methyl fluoride) nicotinic acid and with the A step of embodiment 1 in the 1-that obtains replace the amidate action to halobenzene base-5-amido-1,2,3-triazoles.The nicotinic acid using respectively or the derivant structure of triazole are all similar, therefore the reaction process of example 1A and example 1B part can be used all compounds, use not triazole raw material and the different fluoro nicotinoyl chlorine of equal mole number, at identical reaction conditions (temperature, time, catalyzer), can obtain the target compound of different yields.Finally obtain structure formula III (IV) totally 10 kinds of compounds, result is as shown in table 2:
Table 2 N-(1-replaces halogen substituted-phenyl-1,2,3-triazoles-5-yl) the fluorine-containing replacement niacinamide of-2-
The disclosed 1-of embodiment 1 replaces halobenzene base-5-amido-1,2, the synthetic method feature of 3-triazole is: at intermediate triazene (formula A) active methylene compound of obtaining, close in ring and use alkali alumina to be suspended in (or acetonitrile in aprotic solvent methylene dichloride, benzene, hexanaphthene) under room temperature, stir and spend the night, cyclisation, isomerization is with higher yields synthesising target compound.And conventional method is as sodium ethylate strong alkali catalyst, while making different triazene derivatives close ring generation 1-replacement to halobenzene base-5-amido-1,2,3-triazoles, there is Dimroth and reset.Present method has reduced the generation of resetting derivative impurity, has guaranteed productive rate and the purity of target compound.
Embodiment 2, and the N-of structural formula (V) (5-to fluorophenyl-1,2,4-triazole-3-yl)-2-fluorine niacinamide is synthetic, and R is F, and Rf is F
A, 5-be to fluorophenyl-1, the building-up reactions of 2,4-triazole and step:
A-1, by 11.2 grams of p-Fluorobenzenecarboxaldehydes, 0.09 mole is dissolved in 100 milliliters of benzene, adds 11.5 grams of trifluoroacetyl hydrazines, 0.09 mole, under room temperature, stir 12 hours, obtain 21.1 grams of product trifluoroacetyl group hydrazones, 0.09 mole, except desolventizing, product is not purified can directly be used;
A-2, by 20.0 grams of N-succinic diamide muriates (NCS), 50 milliliters of methylene dichloride of 0.15 mole add 18.6 grams of dimethyl thioethers (DMS) at 0 ℃, 0.30 mole, stirring obtains NCS-DMS complex compound (being called for short Corey-Kim reagent) after half an hour; 21.1 grams of the trifluoroacetyl group hydrazones that A-1 is made, 50 milliliters of dichloromethane solutions of 0.09 mole react 1 hour with NCS-DMS complex compound at-78 ℃, under stirring, slowly rise to room temperature and react 6 hours, making the methyne chloride derivatives solution of trifluoroacetyl hydrazone; After product desolventizes, cross silicagel column, use irrigation sherwood oil: ethyl acetate=98: 2-98: 10, desolventizing obtains 14.8 grams, the muriatic derivative of pure methyne, 0.05 mole;
A-3,50 milliliters of acetonitrile solutions of steps A-2 methyne muriate add 4.8 grams, urea; 10.0 grams of 0.08 mole and excessive triethylamines; under 0.1 mole of room temperature, stir 12 hours; washing desalination trifluoroacetyl hydrazone urea derivative (B) 17.5 grams; 0.06 mole; thick 42.4 grams of excess of sodium carbonate for product; under 100 milliliters of room temperatures of 1: 1 aqueous ethanolic solution of 0.4 mole, stir 2 hours cyclodehydrations and remove protecting group trifluoroacetyl group simultaneously; obtain target compound 5-to fluorophenyl-3-amido-1; 8.4 grams of 2,4-triazoles, fusing point; 125 ℃, yield 78%.
Therefore as previously mentioned, halogen substituted benzaldehyde is had to similar structure, their reactivity worth is essentially identical, can continue to use the intermediate that the A step reaction technique of example 2 obtains, as shown in table 3 target compound:
Table 3 5-replaces halobenzene base-3-amido-1,2,4-triazole
Sequence To halobenzene formaldehyde (raw material) Target compound
3-1 P-Fluorobenzenecarboxaldehyde 5-is to fluorophenyl-3-amido-1,2,4-triazole
3-2 4-chloro-benzaldehyde 5-rubigan-3-amido-1,2,4-triazole
3-3 P-bromobenzaldehyde 5-is to bromophenyl-3-amido-1,2,4-triazole
3-4 To methyl fluoride phenyl aldehyde 5-is to methyl fluoride phenyl-3-amido-1,2,4-triazole
3-5 To difluoromethyl phenyl aldehyde 5-is to difluoromethyl phenyl-3-amido-1,2,4-triazole
Building-up reactions and the step of B, N-(5-to fluorophenyl-1,2,4-triazole-3-yl)-2-fluorine niacinamide:
B-1, by 1.5 grams, the fluorine-based nicotinic acid of 2-, 0.01 mole is added to 6.0 grams of excessive thionyl chlorides, in 0.05 mole, chlorine and sulfurous gas are discharged in reaction at once, notice that water absorbs in order to avoid poisoning, react mild post-heating and reflux 1 hour, decompression, except excessive thionyl chloride, makes acyl chlorides;
B-2,5-that A-3 step is obtained be to fluorophenyl-3-amido-1,1.7 grams of 2,4-triazoles, 30 milliliters of chloroformic solutions of 0.009 mole, are slowly added drop-wise in the fluorine-based nicotinoyl chlorine of the 2-making, after dropwising, continue to stir 30 minutes, desolventize by 1M aqueous sodium hydroxide washes and wash and be neutral;
The extraction of B-3, benzene, dry after with alcohol crystal, after purifying, obtain 2.0 grams of target compound N-(5-to fluorophenyl-1,2,4-triazole-3-yl)-2-fluorine niacinamide colourless crystallizations, fusing point 161.8-162.8 ℃.
The B step reaction of embodiment 2 comprise the different chloride products containing fluoro substituents (fluorine-based and methyl fluoride) nicotinic acid and with A step in the 5-that obtains replace halobenzene base-1, the amidate action of 2,4-triazole.Nicotinic acid and the triazole derivative structure used are respectively all similar, therefore, the technique of the A step of embodiment 2 and B step reaction part can be used all compounds, use not triazole raw material and the different fluoro nicotinoyl chlorine of equal mole number, at identical reaction conditions (temperature, time, catalyzer), can obtain the target compound of different yields.Finally obtain structural formula (V) (VI) totally 10 kinds of changes
Compound, result is as shown in table 4:
Table 4 N-(5-replaces halogen substituted-phenyl-1,2,4-triazole-3-yl) the fluorine-containing replacement niacinamide of-2-
The disclosed 5-of embodiment 2 replaces halobenzene base-3-amido-1, the feature of 2,4-triazole synthetic method is: in the active hydrazone compound building-up process of reactive intermediate trifluoroacetyl hydrazone intermediate (B), use NCS-DMS reagent (Corey-Kim reagent), and can be referring to J.Amer.Chem.Soc., 94,7586 (1972), it is active specy stable under low temperature, effective especially to the chlorination of hydrazone, can be referring to P.S.Fernanes, Tetrahedron, 52,661 (1996); Next has used trifluoroacetyl group as blocking group, and it is also activator simultaneously, and easily hydrolysis under room temperature weak basic condition makes that halobenzene radical derivative is closed to ring generation 5-and replaces halobenzene base-3-amido-1, Dimroth does not occur during 2,4-triazole and reset.Present method has reduced the generation of resetting derivative impurity, has guaranteed productive rate and the purity of target compound.
Foregoing description only proposes as several enforceable technical schemes of synthetic method of the present invention, not as the Single restriction condition to its technical scheme itself.

Claims (8)

1. replace halobenzene base triazole ring is replaced and fluoridizes niacinamide compound, compound structure represents as general formula:
Wherein: A is N-(1-replaces halobenzene base-1,2,3-triazoles)-5-amine groups:
(I);-R is-F ,-Cl ,-Br ,-CFH 2,-CF 2h;
Or
A is N-(5-replaces halobenzene base-1,2,4-triazole)-3-amine groups:
(II);-R is-F ,-Cl ,-Br ,-CFH 2,-CF 2h.
2. according to the replacement described in claim 1, halobenzene base triazole ring is replaced and fluoridizes niacinamide compound, it is characterized in that: the compound of described structure formula I is that (1-replaces halobenzene base-1 N-, 2,3-triazole-5-yl)-2-fluorine niacinamide, wherein the replacement of 1-position is respectively fluorobenzene halobenzene base, to chlorobenzene, to bromobenzene, to methyl fluoride benzene, to benzal fluoride; R ffor-F; Compound structure represents as led to formula III:
3. according to the replacement described in claim 1, halobenzene base triazole ring is replaced and fluoridizes niacinamide compound, it is characterized in that: the compound of described structure formula I is that (1-replaces halobenzene base-1 N-, 2,3-triazole-5-yl)-2-methyl fluoride niacinamide, wherein the replacement of 1-position is respectively fluorobenzene halobenzene base, to chlorobenzene, to bromobenzene, to methyl fluoride benzene, to benzal fluoride; R ffor-CFH 2; Be that compound structure represents as led to formula IV:
4. according to the replacement described in claim 1, halobenzene base triazole ring is replaced and fluoridizes niacinamide compound, it is characterized in that: the compound of described structure formula II is N-(5-substituted-phenyl-1,2,4-triazole-3-yl)-2-fluorine niacinamide, wherein, the replacement of 5-position is respectively fluorobenzene halobenzene base, to chlorobenzene, to bromobenzene, to methyl fluoride benzene, to benzal fluoride; R ffor-F; Compound structure represents as general formula (V):
5. according to the replacement described in claim 1, halobenzene base triazole ring is replaced and fluoridizes niacinamide compound, it is characterized in that: the compound of described structure formula II is N-(5-substituted-phenyl-1,2,4-triazole-3-yl)-2-methyl fluoride niacinamide, wherein, the replacement of 5-position is respectively fluorobenzene halobenzene base, to chlorobenzene, to bromobenzene, to methyl fluoride benzene, to benzal fluoride; R ffor-CFH 2; Compound structure represents as led to formula VI:
6. according to the replacement described in claim 2, halobenzene base triazole ring is replaced the synthetic method of fluoridizing niacinamide compound, wherein the synthesis step of N-(1-is to fluorophenyl-1,2,3-triazoles-5-yl)-2-fluorine niacinamide (III) comprising:
A, synthetic 1-, to fluorophenyl-5-amido-1,2,3-triazoles, react as follows:
A-1, by 1.1 grams of para-fluoroaniline, 0.01 mole is dissolved in 30 milliliters of 2M hydrochloric acid, add 40 ml water dilutions, again by 0.7 gram of Sodium Nitrite, 0.01 mole is dissolved in a small amount of water, and reaction makes diazonium salt solution at 0 ℃, maintains this temperature and drips amido acetonitrilehydrochlorate 1.0g, the 30 ml water solution of 0.01 mole, stirring reaction 2 hours;
A-2, add standing over night after excessive sodium acetate 25-30 gram dissolving, petroleum ether extraction obtains crude product, then recrystallization obtains 1-to 1.9 grams of fluoro-azidophenyl-3-nitrile methyl-triazenes (A), fusing point 95-96 ℃, yield 95% in sherwood oil;
A-3, above-mentioned triazene is dissolved in non-protonic solvent methylene dichloride, add 5 grams of alkali aluminas, it does not dissolve, and within being suspended in solvent, under room temperature, stirring and spends the night, elimination solid, desolventize target compound 1-to 1.6 grams of fluorophenyl-5-amido-1,2,3-triazoles, 130 ℃ of fusing points, yield 80%;
B, synthetic N-(1-is to fluorophenyl-1,2,3-triazoles-5-yl)-2-fluorine niacinamide, react as follows:
B-1, by 1.5 grams, the fluorine-based nicotinic acid of 2-, 0.01 mole, be added to 6.0 grams of excessive thionyl chlorides, in 0.05 mole, chlorine and sulfurous gas are discharged in reaction at once, react mild post-heating and reflux 1 hour, decompression, except excessive thionyl chloride, makes acyl chlorides;
B-2,1-that A-3 is made are to 1.7 grams of fluorophenyl-5-amido-1,2,3-triazoles, 0.009 mole of 30 milliliters of dichloromethane solution, is slowly added drop-wise in the 2-fluorine nicotinoyl chlorine making, and dropwises and continues to stir 30 minutes, desolventize, by 1M aqueous sodium hydroxide washes, wash and be neutral;
B-3, benzene extraction, dry rear with alcohol crystal, purifying obtains 2.4 grams of N-(1-is to fluorophenyl-1,2,3-triazoles-5-yl)-2-fluorine niacinamide colourless crystallization, fusing point 165.2-166.3 ℃.
7. according to the replacement described in claim 4, halobenzene base triazole ring is replaced the synthetic method fluoridize niacinamide compound, wherein the synthesis step of N-(5-to fluorophenyl-1,2,4-triazole-3-yl)-2-fluorine niacinamide (V) comprising:
A, synthetic 5-be to amido-1, fluorophenyl-3, and 2,4-triazole is reacted as follows:
A-1, by 11.2 grams of p-Fluorobenzenecarboxaldehydes, 0.09 mole is dissolved in 100 milliliters of benzene, adds 11.5 grams of trifluoroacetyl hydrazines, 0.09 mole, under room temperature, stir 12 hours, obtain 21.1 grams of product trifluoroacetyl group hydrazones, 0.09 mole, except desolventizing, product is not purified can directly be used;
A-2, by 20.0 grams of N-succinic diamide muriates (NCS), 50 milliliters of methylene dichloride of 0.15 mole add 18.6 grams of dimethyl thioethers (DMS) at 0 ℃, 0.30 mole, obtain NCS-DMS complex compound after stirring half an hour; 21.1 grams of the trifluoroacetyl group hydrazones that A-1 is made, 50 milliliters of dichloromethane solutions of 0.09 mole react 1 hour with NCS-DMS complex compound at-78 ℃, under stirring, slowly rise to room temperature and react 6 hours, making the methyne chloride derivatives solution of trifluoroacetyl hydrazone; After product desolventizes, cross silicagel column, use irrigation sherwood oil: ethyl acetate=98: 2-98: 10, desolventizing obtains 14.8 grams, the muriatic derivative of pure methyne, 0.05 mole;
A-3,50 milliliters of acetonitrile solutions of steps A-2 methyne muriate add 4.8 grams, urea, and 10.0 grams of 0.08 mole and excessive triethylamines, stir 12 hours under 0.1 mole of room temperature, and washing desalination obtains structure
17.5 grams of the trifluoroacetyl hydrazone urea derivatives of formula (B); 0.06 mole; thick 42.4 grams of excess of sodium carbonate for product; under 100 milliliters of room temperatures of 1: 1 aqueous ethanolic solution of 0.4 mole, stir 2 hours cyclodehydrations and remove protecting group trifluoroacetyl group simultaneously, obtaining target compound 5-to fluorophenyl-3-amido-1,2; 8.4 grams of 4-triazoles; fusing point, 125 ℃, yield 78%.
B, synthetic N-(5-to fluorophenyl-1,2,4-triazole-3-yl)-2-fluorine niacinamide, reacts as follows:
B-1, by 1.5 grams, the fluorine-based nicotinic acid of 2-, 0.01 mole is added to 6.0 grams of excessive thionyl chlorides, in 0.05 mole, chlorine and sulfurous gas are discharged in reaction at once, notice that water absorbs in order to avoid poisoning, react mild post-heating and reflux 1 hour, decompression, except excessive thionyl chloride, makes acyl chlorides;
B-2,5-that A-3 step is obtained be to fluorophenyl-3-amido-1,1.7 grams of 2,4-triazoles, 30 milliliters of chloroformic solutions of 0.009 mole, are slowly added drop-wise in the fluorine-based nicotinoyl chlorine of the 2-making, after dropwising, continue to stir 30 minutes, desolventize by 1M aqueous sodium hydroxide washes and wash and be neutral;
The extraction of B-3, benzene, dry after with alcohol crystal, after purifying, obtain 2.0 grams of target compound N-(5-to fluorophenyl-1,2,4-triazole-3-yl)-2-fluorine niacinamide colourless crystallizations, fusing point 161.8-162.8 ℃.
8. according to the replacement described in claim 1, halobenzene base triazole ring is replaced the purposes fluoridize niacinamide compound, it is characterized in that: for effective constituent or the ancillary component of agricultural bactericidal preparation or make mixed preparation with other effective constituents.
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